The goal of this research is to validate and optimize an integrated magnetic resonance (MR) approach that can noninvasively determine coronary flow reserve and myocardial oxygenation in ischemic heart disease. Our real time MR approach uses the simultaneous acquisition of time-of-flight (TOF) coronary artery velocity measurements and blood-oxygenation level dependent (BOLD) assessment of myocardial oxygenation. Our modified TOF MR tomographic approach measures coronary flow velocity using the intrinsic contrast generated by flowing blood. Our preliminary data demonstrate normal coronary reserve index during vasodilator challenge in normal volunteers, and abnormal flow responses in patients with obstructive coronary lesions. Following optimization in animals, data will be acquired in normal volunteers and in patients with focal coronary artery disease (CAD), with Doppler flow reserve correlation in the latter. Characterization of the physiological significance of coronary lesions will be enhanced by the simultaneous acquisition of images sensitive to changes in myocardial oxygen consumption. We will exploit the intrinsic sensitivity of MR to changes in deoxyhemoglobin content, thereby producing T2*contrast. This susceptibility contrast in the heart depends on may parameters including coronary flow, hemoglobin content, coronary venous volume, and local myocardial metabolism (oxygen consumption). We will develop both the theory and experimental techniques required to translate the changes we observe in MR images into changes in local physiological variables. We will combine computer simulations, that have already proven successful in explaining MR changes with brain activation, with novel experiments on isolated blood-perfused heats, using EPI in order to quantify these changes in vivo. Once optimized, data on regional myocardial perfusion will be acquired in normal volunteers and in patients with focal coronary disease, using positron emission tomography (PET) for comparison on the latter. Our overall objectives are both to improve imaging of the macroscopic and microscopic blood supply of the heart and to gain a better understanding of the role of coronary flow limitation in the pathogenesis and clinical evolution of ischemic heart disease. The long term goal of this research is to develop a protocol that integrates these approaches into a single cardiac MR exam.